Title:Arginine-Glycine-Aspartic Acid-anchored Curcumin-based Nanotherapeutics
Inhibit Pyroptosis-induced Cytokine Release Syndrome for In Vivo and In Vitro
Sepsis Applications
Volume: 29
Issue: 4
Author(s): Yi Shi, Qian Wu, Yi Lu, Ling-Peng Meng, Xiao-Ling Xu*, Xiao-Juan Wang and Wei Chen*
Affiliation:
- Department
of Functional Education and Research, Shulan International Medical College, Zhejiang Shuren University, Hangzhou,
310015, PR China
- ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR China
Keywords:
Sepsis, pyroptosis, macrophages, RGD-modified liposome, curcumin, cytokine.
Abstract:
Aim: We aimed to design RGD-anchored liposomes encapsulating an antipyroptosis drug that could
efficiently target macrophages and relieve the rate of cytokine release syndrome, providing a new strategy for
sepsis treatment, especially sepsis-induced acute renal injury.
Background: Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by host response disorders
due to infection. Sepsis has a high incidence and remains one of the leading causes of death worldwide.
Objective: Macrophage-mediated pyroptosis plays an important role in the occurrence and development of cytokine
release syndrome and organ injury caused by sepsis. Curcumin can inhibit inflammasome assembly and
slow the progression of pyroptosis by scavenging intracellular reactive oxygen species, but it has poor water solubility
and low bioavailability. The emergence of drug-delivery nanosystems has overcome this problem, but
there is still a lack of research on how to accurately deliver antipyroptotic drugs to innate immune cells and subsequently
hinder pyroptosis.
Methods: We constructed a curcumin-loaded RGD-modified liposome (RGD-lipo/Cur) and demonstrated that
RGD-lipo/Cur could effectively target macrophages.
Results: In vitro, RGD-lipo/Cur reduced the upregulation of caspase-1, caspase-3, NLRP3, IL-1β and GSDMD,
inhibiting pyroptosis, reducing oxidative stress, and attenuating the proinflammatory cytokine cascade.
Conclusion: RGD-lipo/Cur was considered to have great potential for sepsis treatment.
